Background/Purpose: Elevated expression of interferon(IFN)-regulated genes in peripheral blood cells has been reported in systemic lupus erythematosus (SLE) patients and is known as the IFN signature. The IFN signature in SLE has been reported to be correlated with disease-related autoantibodies such as anti-dsDNA and anti-RNP and with disease activity. Differential expression of the IFN signature among SLE patients has been reported and may indicate that the patient subgroups categorized with IFN signature expression levels have distinct biological differences. We determined the IFN signature using a 3-gene surrogate for the expression of the IFN-regulated genes¹⁾ and serological biomarkers described below in Japanese SLE patients. We compared these results to reported values for non-Japanese SLE populations²⁾.

Methods: Peripheral blood samples from healthy volunteers (HVs) and SLE patients were analyzed in Japanese and American/European¹⁾populations. SLE patients with SELENA-SLEDAI (SS) score >6 and without active renal nephritis, CNS or hematological disease were eligible. Three IFN-regulated genes (EPSTI1, HERC5 and TYK1) were chosen to represent the overall IFN signature of IFN-regulated genes, and the standardized average values of PCR quanitified expression of the three genes are reported as the IFN signature metric (ISM) score. The titers of auto-antibodies and serological markers (C3, C4, anti-dsDNA, anti-RNP, ANA, ENA and serum BAFF) were measured from the same patients.

Results: The mean of ISM scores in HVs were lower than in the SLE patients. The ISM score distribution range of HVs was higher in Japanese (n=20) than in non-Japanese (n=60); the ISM score at the 95 percentile of distribution was 1.7 and 1.0, respectively. The mean of ISM score of Japanese SLE patients (n=60, SS score 8.9±2.3) was 2.9±1.1, which is higher than in non-Japanese SLE patients (2.0±1.5) with similar disease activity(n=238, White n=76, Black n=34, Hispanic n=114, other n=14, SS score 9.8±3.3). ISM scores in non-Japanese patients showed correlations with anti-dsDNA titer, positive ENA, serum BAFF levels, hypocomplementemia and SS score. In contrast, ISM scores in Japanese patients were generally high as a whole population, and did not correlate with these findings. Although the frequency of anti-dsDNA antibody positive patients was comparable between the two populations, the median (IQR) titer was lower in Japanese [34 IU/mL (28- 76)] than non-Japanese patients [53 IU/mL (14-193)¹⁾]. Serum BAFF correlated with ISM scores in non-Japanese SLE patients but not in Japanese patients. The profiles in ISM and serological abnormality (SA) in two ethnic populations demonstrated a contrast; high ISM/ high SA or low ISM/ low SA in non-Japanese versus high ISM/ low SA in Japanese patients.

Conclusion: The differences in ISM and SA profiles between Japanese and non-Japanese SLE patients suggests that there are demographic differences in molecular pathophysiology of SLE. These differences may have implications for therapeutic interventions that target the innate and/or adaptive immune system.

¹⁾ submitted

²⁾ Kalunian KC, et al. (submitted) 

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/interferon-gene-signature-expression-and-serological-differences-in-japanese-and-non-japanese-sle-patients/